Bioresorbable patent foramen ovale closure—is less more?

In patients with prior cryptogenic stroke, percutaneous patent foramen ovale (PFO) closure using self-expanding double-discs are superior in preventing recurrent events compared to medical therapy alone (1-4). Registries and randomized trials have demonstrated high rates of procedural success (>90%) and extremely low rates of serious complications (<1%). Potential periprocedural complications include device embolization and access related bleeding. Possible complications during follow-up include device-related thrombosis, arrhythmia, aortic vessel wall erosion, endocarditis. These risks are very rare (1). Nevertheless, they are important to consider as PFO closure is often performed in otherwise healthy, young patients with long life expectancy.

A few companies are working on the development of bioresorbable occluders. A fully resorbable device leaves nothing behind, might further reduce adverse events and facilitate transseptal puncture for future interventions such as pulmonary vein isolation, left atrial appendage occlusion, or mitral edge-to-edge reconstruction.

In a recent issue of Circulation, Zhang et al. (5) report a prospective, multicenter, randomized noninferiority trial comparing a novel fully biodegradable PFO closure device with a conventional nitinol-based PFO occluder in 190 patients across seven centers in China. The primary efficacy end point was closure success at 6 months, defined as right-to-left shunt (RLS) grade 0 or 1 on contrast echocardiography. In the intention-to-treat analysis, successful closure was achieved in 91% of patients in the biodegradable device group and 92% in the nitinol group. Efficacy was maintained during 24-month follow-up, with successful closure (RLS grade 0 or 1) reported in 95% of the biodegradable group and 92% of the control group. These endpoints were blindly assessed by a core laboratory, one of the strengths of the trial. The observed primary endpoint rate for the nitinol device was within the expected range for the Amplatzer PFO closure device, which is widely regarded as the gold standard (6,7). Another strength of the trial was the 24-month follow-up, demonstrating sustained mid-term efficacy and safety results.

Although the number of patients was low, safety profile of the device appeared to be favorable: no deaths, embolic events, device-related thrombus, or erosions were observed in either group, and there was no difference in arrhythmia rates. Of note one patient in the biodegradable group required surgical removal because of intraprocedural deformation related to insufficient device locking. The authors state that this was likely caused by inexperience of the operator.

As the occluder is not radiopaque, implantation was performed with echocardiographic guidance. While transthoracic echocardiography may be possible in some patients, transesophageal echocardiography appears to be the logical and preferred imaging modality. Some operators are used to performing PFO occlusion under fluoroscopy without the need for patient sedation and transesophageal echocardiography (8,9). Such centers would have to adjust their protocols. However, in the U.S., most implantations are performed using intravascular ultrasound (ICE).

We would like to congratulate the authors on this original and innovative study.

They show that a biodegradable PFO-occluder can achieve closure rates similar to contemporary nitinol-based devices (1,2,4,8). Regarding safety events, 100 patients may not be enough to detect rare, but potentially catastrophic events such as erosion of the aortic wall. Therefore, more data are required to draw firm conclusions regarding short- and long-term safety profile of the device.

Bioresorbable PFO occlusion: a new standard or just a gimmick?

The concept of bioresorbable PFO closure is easy to understand for physicians and patients: no permanent material left behind, potentially fewer long-term complications, preserved transseptal access. Indeed, a permanent double-disc device across the interatrial septum might complicate future transseptal access (10). However, a transseptal puncture should still be possible but may require a more posterior puncture (which is preferred for many procedures anyway). On the other hand, we are not aware of any patient where a transseptal puncture was performed across a previously implanted bioresorbable occluder. Bioresorbable technology in humans remains incompletely understood and the experience with bioresorbable coronary scaffolds teaches caution (11). While initial studies yielded promising results, subsequent registries and case reports have painted a different picture with early scaffold collapse, variable rates of bioabsorbtion and late target lesion failure. The claim that an aorto-coronary bypass graft can be safely sutured later onto an artery previously treated with resorbable scaffolds, still needs to be proven. Bioprosthetic aortic valve restenosis behaves differently than native aortic valve stenosis. Therefore, the properties of the bioresorbable PFO occluder tissue must be very carefully evaluated by ex vivo and imaging to assure the tissue response to puncture.

Like drug eluting stents, the bar is high in PFO occlusion. Nitinol-based occluders have proven to be very durable and safe, the material is flexible despite a good stiffness and widely used by interventional cardiologists and other specialties. Polydioxanone or poly-L-lactic acid, the material bioresorbable occluders are made of, however, is less flexible and less stiff than nickel-titanium. Therefore, after being elongated in the delivery catheter, bioresorbable occluders assume a more lantern-like shape. To overcome these limitations, a central locking mechanism is required, holding the two discs close together. The occluder is locked before final release. Such a lock might increase the risk for aortic wall/aortic sinus of Valsalva erosion or perforation by reducing flexibility of the device. Although no such events were observed in the study by Zhang et al., more patients are required to rule out the risk for such rare, but potentially dangerous complications. PFO occlusion is a prophylactic procedure often performed in young and healthy adults. Therefore, even a 1:500 risk of such a complication may lead to a complete discontinuation of the device.

Research has shown that metallic occluders may alter left atrial reservoir, conduit and contraction function (12). The effect of bioresorbable occluders on atrial function is unknown. Furthermore, endothelialization may be earlier or later, depending on the design of the device (13). Another treatment option that does not alter blood flow and requires almost no endothelialization is suture-based PFO closure. Registry data of 703 patients has recently been published demonstrating that excellent results over a median of 4 years of follow-up can be achieved in experienced hands (14).

What is needed

Multicenter registries with long-term follow-up are required to assess rare adverse events and durability beyond 24 months, including the time after potential device resorption. Standardized rhythm monitoring should better define arrhythmia burden, and learning-curve analyses should clarify operator thresholds and training requirements, as operator experience may influence outcomes as much as biomaterial properties. An important future endpoint is the feasibility of transseptal intervention after bioresorbable PFO closure. If the bioresorbable device preserves a more natural septal substrate for left atrial access, this could offer a meaningful advantage, particularly in younger patients. Demonstrating this will require longitudinal studies to later procedures through registries or device surveillance networks.

Conclusions

Zhang et al. provide important randomized multicenter evidence that a novel bioresorbable PFO occluder can achieve closure efficacy outcomes noninferior to those of a conventional nitinol device, without signals of adverse short- to mid-term safety, while showing echocardiographic resorption over 24 months. Although these findings do not establish a new gold standard, they support the credibility of the concept, a meaningful advance in a field dominated by permanent metal implants. If larger studies confirm long-term safety, durable closure after resorption, and reproducibility across centers, the key question will potentially shift from whether bioresorbable PFO closure is feasible to which patients are most likely to benefit from the new technology. Let us assume that we have a completely biodegradable PFO occluder available that has the same safety and efficacy profile as a nickel-titanium based device, with comparable costs. We have no doubt that most patients and most physicians will prefer the resorbable device over the metallic one. Therefore, in summary, we believe that a bioresorbable shunt occluder has a potential role for routine use in the catheterization laboratory, but clearly, more data is required to establish safety and long-term durability of such devices.

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.